SUMMARY OF WORK The role of environmental and behavioral factoirs in the development of chronic hypertension remains to be clarified. Experimental studies with laboratory animals have shown that aversive conditioning that induces respiratory suppression and increases pCO2 decreases renal excretion of sodium and leads to progressive hypertension in sodium-loaded subjects. Studies with healthy humans have shown that voluntary hypopnea for 30 min that increases pCO2 also decreases renal sodium excretion and increases plasma concentrations of natriuretic hormones that are sensitive to expansion of plasma volume. In addition, studies have shown that the resting and 24-hr ambulatory blood pressure of normotensive humans with high resting end tidal CO2 (PetCO2) is more responsive to high sodium diet than matched controls with lower resting PetCO2.Over the past year, we have found in studies with the Baltimore Longitudinal Study on Aging that mean resting PetCO2 of women in blue collar occupations was higher than that of women in white collar occupations. No such effects were observed in men. In addition, we found that women with high resting PetCO2 had higher plasma concentrations of an endogenous digitalis-like factor, marinobufagenin, than women with lower resting PetCO2. Moreover, we found that women with high resting PetCO2 had greater carotid artery intima-media thickness than women with low resting PetCO2. This association was independent of the association of PetCO2 with blood pressure. Again, no such association was found in men. Taken together, these studies support the view that the set point for pCO2 is responsive to an environmental condition, that it is associated with increased plasma volume, and that it can have structural cardiovascular effects that may be relevant to the origins of sodium sensitive forms of hypertension in women. Studies are needed to determine the origins of the gender differences in the association of pCO2 with cardiovascular structure and function.